tbuckley/cabot-search huggingface dataset:
PB2039: INFLAMMATORY MARKERS IN HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS - A SINGLE CENTRE STUDY
Authors: Mariam Goubran, Caroline Spaner, Amanda LI, Adi Zoref-Lorenz, Michael Jordan, Luke Y C Chen, Audi Setiadi
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathological immune activation that can be difficult to distinguish from other cytokine storm syndromes such as Adult-Onset Still’s disease (AOSD) and COVID-19 cytokine storm (CCS). The HLH-2004 criteria and HScore are the best available diagnostic criteria but have important limitations. Many of the tests included in the current HLH-2004 criteria, such as flow cytometry for NK cell cytotoxicity and cytokine analysis, are only available in specialized centers, and while useful in pediatric HLH, are less so in adult HLH which is characterized by hyperinflammation. Inflammatory markers such as ferritin, are not specific for HLH and can be seen in several hyperinflammatory syndromes. We sought to examine the clinical utility of a simply, readily available inflammatory marker, C-reactive protein CRP) in combination with sIL2r levels in distinguishing HLH from two similar cytokine storm syndromes, AOSD and CCS. Aims: Our aim is to analyze patterns of elevation in CRP and sIL2r to help clinicians in the differential diagnosis of HLH, AOSD, and CCS. Methods: A retrospective chart review was conducted for 61 patients with secondary HLH, 10 patients with AOSD, and 13 patients with CCS. Demographic data as well as inflammatory biomarkers including CRP and sIL2r levels were collected if drawn within 72 hours of the acute episode that led to diagnosis, and prior to treatment. The Kruskal-Wallis test was used to compare CRP in the HLH, AOSD, and CCS groups, as well as to compare CRP in HLH subgroups by underlying trigger (infection, malignancy, autoimmune, and idiopathic). The Kruskal-Wallis test was also used to measure and compare sIL2r levels in the HLH group compared to AOSD, as well as by HLH subtype. Results: C-reactive protein is significantly lower in secondary HLH (Mdn = 76.4) compared to AOSD (Mdn = 114.5, p = 0.039) and CCS (Mdn = 121.0, p = 0.003). When analyzed by subtype, CRP levels in malignancy-associated HLH (MAHS) were not significantly different than AOSD or CCS, while CRP levels were significantly lower in the non-MAHS groups (Mdn = 58.9, p = 0.01) compared to AOSD and CCS (p <0.001), particularly when compared to infection-associated HLH (IAHS) (Mdn = 32.7, p = 0.009). Soluble IL2 receptor levels were significantly higher in the HLH group (Mdn = 7436.0, p = 0.03) compared to AOSD (Mdn = 2252.0). Summary/Conclusion: C-reactive protein is significantly lower in HLH compared to AOSD and CCS, specifically in non-MAHS, and may be a useful and easily accessible biomarker aiding in the differential diagnosis of HLH. Soluble IL2 receptor levels are a useful biomarker in distinguishing AOSD from HLH, as it is not as significantly elevated in AOSD. Keywords: Macrophage, Inflammation, IL-6, Cytokine
PB2032: FACTORS ASSOCIATED WITH TRANSFUSION INDEPENDENCY POST TREATMENT IN HIGH RISK MDS PATIENTS
Authors: Naveena Fatima, Anum Khalid, Laraib Majeed, Nida Anwar
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: One of the potential advances in the treatment of high risk myelodysplastic syndromes (MDS) has been the use of hypomethylating agents (HMA) in combination with the Bcl-2 inhibitor venetoclax (VEN). This therapy has been found to be expedient in patients who never achieve hematological recovery and experience morbidity and quality of life problems as a result of repeated transfusions, infections, and hospitalizations. Aims: The study was conducted to observe the factors associated with transfusion independence post treatment with HMA-VEN therapy in high risk MDS patients. Methods: We analyzed 19 high risk MDS patients who received treatment with HMA i.e. decitabine or azacitidine, along with VEN. Chi square and Mann Whitney U test were performed and p-value <0.05 was considered significant. Results: Median age of patients was 50(23-69) years with male predominance 14 (74%). Median total leucocyte count (TLC), hemoglobin (Hb), platelet count (PC) and blast cells (BC) at baseline was 9.6 x10^9/L, 8.8g/dL, 27 x10^9/ and 42% respectively. However; after median 3 (1-12) HMA-VEN cycles, they were 3.41 x10^9/L, 9.6g/dL, 31 x10^9/L and 1% respectively. Transfusion dependency was observed in 16(84%) patients pre-treatment and it was resolved in 8(42%) patients post-treatment. Overall, complete response (CR) was achieved in 7(37%) patients. The transfusion independency post treatment was observed with age, gender, cytogenetics, response, TLC, Hb, PC, BC and number of cycles and it was observed that patient who achieved the response and who received 5 (1-12) HMA-VEN cycles became transfusion independent (p=<0.05). Summary/Conclusion: In conclusion, our study revealed that treatment response and number of cycles were significantly associated with the post treatment transfusion independency. Transfusion is associated with complications and it is important to address the factors that may have an impact on transfusion independence and improve the quality of life of patients. Further longitudinal studies with larger sample size are needed in this regard. Keywords: Treatment, MDS, Transfusion
P1668: NON-APOPTOTIC CIRCULATING MICROPARTICLES ARE INVERSELY ASSOCIATED WITH PROCOAGULANT BIOMARKERS IN PATIENTS WITH ACUTE CORONARY SYNDROMES
Authors: Zoi Pallantza, Nikolaos Papageorgiou, Efimia Zacharia, Dimitrios Tousoulis, Konstantinos Tsioufis
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Circulating apoptotic microparticles (MPs) have been considered as markers of ongoing thrombogenesis by a number of studies. However, their potential association with biomarkers of coagulation in patients with acute coronary syndromes (ACS) has not been fully determined yet. Aims: To assess the potential correlation of circulating MPs with levels of fibrinogen, d-dimers and INR in patients presenting with a recent ACS. Methods: The present study included 49 patients with STEMI, 35 with NSTEMI and 33 with UA. 15 patients with stable coronary artery disease and 16 healthy subjects served as controls. Citrated blood samples were obtained from peripheral veins within 12-24 hours from hospital admission. Circulating endothelial (CD144+)-EMPs, red blood cell- (CD253+)-RMPs and platelet-derived (CD41+)-PMPs and their annexin-V binding capacity (phosphatidylserine+-PS+) were determined by flow cytometry. The levels of fibrinogen, d-dimers and INR were assessed by standard coagulometry methods. Results: In patients with STEMI, INR was negatively correlated with the levels of total annexin-binding apoptotic microparticles (r=-0.381, p=0.20) and the levels of PS+EMPs (r=-0.444, p=0.006). Importantly, in patients with NSTEMI, a negative correlation was noted between all measured subtypes of circulating MPs and the levels of fibrinogen, with the strongest negative correlation noted in PS+PMPs (total PS+MPs: r=-410, p=0.015; PS+EMPs: r=-0.398,p=0.018; PS-EMPs: r=-0.334, p=0.05; PS+RMPs r=-0.364, p=0.032; PS-RMPs r= -0.361, p=0.033; PS+PMPs r=-0.498, p=0.002; PS-PMPs r= -0.357, p=0.035). In the group of patients with UA, significant negative associations were noted between the levels of d-dimers and PS-EMPs (r=-0.356, p=0.046) and PS-RMPs (r=-0.358, p=0.044). Summary/Conclusion: We have found that, in patients with STEMI, the levels of apoptotic MPs are negatively correlated with the levels of INR which supports the existing evidence of their procoagulant activity. The negative correlation noted between the levels of apoptotic MPs and fibrinogen in patients with NSTEMI could be due to the sequestration of apoptotic MPs in sites of atherothrombosis. However, the negative correlation of non-apoptotic MPs with markers of thrombosis in patients with UA may reflect an actual, counterbalancing, antithrombotic effect of the non-apoptotic MPs. The apoptotic and non-apoptotic MPs may affect thrombogenesis via two discrete and opposing pathways that have not been fully explored yet. Keywords: D-dimer, Coagulation, Thrombosis
PB2563: IRON DEFICIENCY ANEMIA: A MONOCENTRIC EXPERIENCE OF THE HAEMATOLOGY DEPARTMENT OF MONASTIR, TUNISIA
Authors: Donia Bouhoula, Wiem Boufrikha, Laabidi Baraa, Sana Lakhel, Slama Nader, Sarra Boukhriss, Zaineb Mlayah, Adnene Laatiri
Journal: HemaSphere (2023)

Topic: 29. Iron metabolism, deficiency and overload Background: Iron deficiency anemia (IDA) is a public health problem affecting children, adults and the elderly. There are multiple symptoms and etiologies that lead to iron deficiency (ID) that may coexist and challenge the diagnosis. The management of IDA depends on the cause of ID. Aims: The aim is to study the clinical features, etiologies and the management of IDA in our study population. Methods: This retrospective descriptive study included all IDA diagnosed between 2019 and 2021, in the Haematology Department of Monastir, Tunisia; having an etiological investigation or not. Results: Three hundred and sixty-six patients diagnosed with IDA were identified during the study period. The mean age at diagnosis was 48.7 years (range: 39-56). We noted a female predominance with a sex ratio M/F at 0.31. The main symptoms were variable and depended on the severity of its onset: fatigue (96.9%), signs of sideropenia (87.6%), shortness of breath (29%) and pallor (74.8%). Three main mechanisms of IDA were noted: decreased iron absorption (18%), repeated blood loss (77%), and increased iron requirements (5%). The treatment was based on oral iron therapy in the majority of cases (97%), parenteral iron (2%), and transfusion (1%) in patients with severe IDA onset. Among the 366 patients diagnosed with IDA, 147 had upper abdominal pain (40%). An upper gastrointestinal endoscopy had shown gastritis in 126 cases (34%) of which 117 patient (92.8%) had Helicobacter Pylori gastritis. In patients with Helicobacter Pylori gastritis, the IDA was initially refractory to oral iron supplementation therapy in 68% of cases. The eradication of the bacteria resolved the IDA on a long term in 62% and the parenteral iron supplementation was required in 6% of cases. Unsatisfied results were associated with insufficient treatment of the etiology and with therapeutic non-compliance. Summary/Conclusion: Compared to the literature, the digestive cause remains the dominant etiology of IDA. The therapeutic component is based on oral iron supplementation and the management of the etiology. Keywords: Iron deficiency, Iron deficiency anemia, Helicobacter pylori
PB1953: TWELVE CASES OF MULTICENTRIC CASTLEMAN DISEASE WITH ELEVATED SERUM IGG4 LEVELS AND INFILTRATING IGG4 POSITIVE PLASMA CELLS PATHOLOGICALLY FROM A SINGLE CENTER.
Authors: Shishuo Dai, Yu Wu
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Multicentric Castleman’s disease (MCD), classified as Tumor-like lesions with B-cell predominance, is a rare systemic and progressive disease with lymphadenopathy involved multiple lymph nodes. Patients presenting elevation of serum IgG4 levels and infiltrating IgG4 positive plasma cells in lesions should be carefully differentiated from IgG4-related disease (IgG4-RD) in diagnosing MCD. Aims: This study aimed to describe a 12 patients’ cohort with the diagnosis of MCD, which could also fulfil the comprehensive diagnostic criteria for IgG4-RD. Methods: A retrospective medical record review was conducted on all patients diagnosed with MCD in our hospital from January 2010 to December 2022. Inclusion criteria of the cohort: (1) serology: IgG4 concentration> 1350 mg/L, and (2) pathology: number of IgG4+ cells/high-power field ≥10. Clinical manifestations, laboratory examinations, pathological evidence, and treatment details of the cohort were provided. Results: Twelve MCD patients were identified, 3 (25%) females and 9 (75%) males. Median age of diagnosis was 46.5 years (range, 21 - 72 years) with 10 (83.3%) patients being younger than age of 60 years. The most frequent manifestation was recurrent fever (temperature > 38°C) presented in 5 (41.7%) patients; other symptoms included night sweats (25%), weight loss (16.7%), and fatigue (66.7%). Violaceous papules were investigated in 2 (16.7%) patients. Anemia (hemoglobin <100 g/L) was found in 11 (91.7%) patients, thrombocytopenia/thrombocytosis (platelet count <150 k/mL or >400 k/mL) in 8 (66.7%), hypoalbuminemia (albumin <3.5 g/dL) in 10 (83.3%), proteinuria (total protein >10 mg/100 ml) in 3 (25%), elevated C-reactive protein (>10 mg/L) in 8 (66.7%) and interleukin-6 in 11 (91.7%). The median serum IgG4 level was 5 585 mg/L (range 1 690 – 33 000 mg/L). Pathological diagnosis of IgG4-RD preferred were presented in 5 (41.7%) patients. Glucocorticoids monotherapy was given in 5 (41.7%) patients before they diagnosed with MCD. Three (25%) patients received Tocilizumab therapy for MCD. Other therapies consisted of TD, CTX + dexamethasone, TCP/TCD, Rituximab and BD. The median follow-up of all patients was 19.8 (range, 1.47-84.13) months. All patient were alive at the time of data collection. Summary/Conclusion: While pathological diagnosis was vague, clinical manifestation and response to glucocorticoids monotherapy were valuable for differentiated from IgG4-related disease (IgG4-RD) in diagnosing MCD. In this small cohort, most MCD manifested anemia (91.7%) and elevated interleukin-6 (91.7%). The treatment for MCD was heterogeneous with a favorable outcome in this study. Keywords: IL-6, Clinical data, Castleman’s disease
PB1839: CYTOGENETIC PROFILE OF ACUTE MYELOBLASTIC LEUKEMIA TREATED AT THE MOHAMMED V MILITARY HOSPITAL IN RABAT (MOROCCO).
Authors: Moussa Bouh Hawa, Oumayma Hari, Afodome Apolinaire, Yossra Aghoutane, El Mehdi Mahtat, Selim Jennane, Hicham El Maaroufi, Doghmi Kamal
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Cytogenetic is of prognostic interest and an indispensable therapeutic stratification tool in the management of acute myeloid leukemia. Aims: Describe the cytogenetic profile of acute myeloblastic leukemia’s (AML) treated in the Clinical Hematology Department of the Military Hospital (HMIMV) of Rabat. Methods: We analyzed the cytogenetic profiles of patients older than 16 years followed for the acute myeloblastic leukemia (excluding APL) in the Clinical Hematology Department of the HMIMV over an 18-year period from May 2006 to February 2023. Results: 103 records were reviewed. The karyotype was systematically performed in all patients at diagnosis, it was in failure in 12 patients (11.6%), normal in 37 patients (36%) and a clonal abnormality was detected in 54 patients (52.4%). Cytogenetic abnormalities were divided into 3 groups according to ELN 2022 classification (favorable, intermediate and unfavorable); the intermediate risk group was predominant (56.3%) divided into normal karyotype in 37 patients (36%), Trisomy 8 in six patients(5.8%), t(9;11), t(8; 22), monosomy 20, monosomy 15, del 11q23, del y, Add 16, add 21, trisomy 11q, del 6q in one patient each and del17q and del 20q in two patients respectively; followed by the group with unfavorable cytogenetic risk in 21 patients (20%) divided into complex karyotype in 13 patients (12.6%), deletion of chromosome 7q in 5 patients (5%), t (9-22) in 2 patients and deletion 5q in one patient. Twelve patients (11%) had favorable risk cytogenetics consisting of a t(8-21) in 7 patients (6.7%) and an inversion 16 in 5 patients respectively. Intermediate risk cytogenetics was predominant in our patients. Summary/Conclusion: Despite the small number of patients in this mono-centric study, we note the frequency of intermediate cytogenetic risk obliging the clinician to perform molecular biology to refine the prognosis. This result is comparable to those found in the literature. Keywords: AML
PB1785: FOCUSCOPE: A MULTIOMICS SOLUTION TO SIMULTANEOUSLY ANALYZE GENETIC VARIANTS AND TRANSCRIPTOMES IN SINGLE CELLS IN LEUKEMIA
Authors: Murat Seker
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Tumor tissues are known to contain cell-specific genetic variations and gene expression profiles that play a role in the etiology, pathogenesis and treatment outcomes of the diseases. Single-cell sequencing is a powerful tool that has the potential to revolutionize personalized medicine by providing a more detailed and accurate understanding of individual patient biology. Recent advances in high-throughput single-cell sequencing technologies have greatly improved our understanding of complex biological systems. Aims: However, most current high-throughput single-cell sequencing methods detect only gene expression levels. The information on important genetic variants including mutation or fusion is not captured. To better understand the mechanisms of tumor responses to systematic therapy, it is essential to decipher the connection between genotype and gene expression patterns of both tumor cells and cells in the tumor microenvironment. Methods: To address this limitation, we have developed FocuSCOPE, a high-throughput multi-omics sequencing solution capable of simultaneously detecting common genetic variants seen in leukemia and transcriptome from single cells thus delivering more comprehensive insights into each individual cell. The FocuSCOPE technology is centered around specifically designed barcoding beads that can effectively capture both transcriptome and the region of interest and the SCOPE-chip®, a portable microfluidic chip that integrates multiple steps of processing workflow which can be operated manually. Results: Here we used FocuSCOPE on different cell lines to detect druggable TP53, KRAS mutations together with BCR-ABL1 and PML-RARA gene fusions. Summary/Conclusion: FocuSCOPE can be used to detect genetic variants, fusion genes together with whole transcriptome. Keywords: BCR-ABL, PML-RAR, Single nucleotide polymorphism, TP53
PB1891: EARLY DEATH IN ACUTE PROMYELOCYTIC LEUKEMIA IN SOUTHERN TUNISIA
Authors: Asma Koubaa, Olfa Kassar, Maha Charfi, Yousra Fakhfakh Derbel, Faten Kallel, Imen Frikha, Imen Ben Amor, Latifa Khalifa, Rahma Mallek, Moez Medhaffar, Sondes Hdiji, Moez Elloumi
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Despite the improvement treatment in acute promyelocytic leukemia (APL), early death rate, 30 days following the diagnosis, remained higher (14 à 40%). Aims: We reported in this study, clinical and biological characteristic of patients with APL, died early. Methods: Our retrospective study concerned all patients with APL with the diagnosis of APL and followed in the hematology department of Hedi Chaker Hospital Sfax, from January 2000 until December 2019. The diagnosis of APL is based on morphological, cytogenetic and molecular study. The treatment is based on all-trans retinoic acid (ATRA) and chemotherapy regimens. We included patients died early 30 days following the diagnosis. Results: Among 79 patients with APL, twenty three patients died early (30% of cases). The median age was 31 years (extreme: 2-75 years) with sex ratio 1,3. Obesity with BMI more than 25 was noted in 65% of cases. An average delay between symptoms and diagnosis was 10 days. Hyperleukocytosis more than 10000/mm3 (high risk group) was noted in 78% of cases. Thrombopenia (platelets<40000/mm3) was noted in 91% of cases, with disseminated intravascular coagulation (DIC) founded in the majority of cases (96% of cases). Nineteen patients (83%) had hemorrhage syndrome at diagnosis. Eight patients died before treatment, between one and two days of diagnosis. Fifteen patients died early during the induction course before evaluation with an average delay of 8 days (extreme: 2-28). Causes of death before treatment were haemorrhage in seven cases (87.5%). Causes of death during treatment were multiple: respiratory disease due to the differentiation syndrome, a severe haemorrhagic syndrome and or septic shock. Summary/Conclusion: Early death rate is similar to that reported in the literature. Older age, hyper-leukocyte forms, DIC and delay in diagnosis were risk factors in our study. Early diagnosis of APL is essential to reduce the mortality rate and improve overall survival, by establishing early support treatment and administration ATRA therapy as soon as the diagnosis is suspected. By the other way, the use of combined ATRA and arsenic trioxide without chemotherapy, in non-high-risk patients could be an alternative to reduce hematology toxicity and early death rate. Keywords: Hemorrhage, Mortality, Acute promyelocytic leukemia
PB1898: FIVE-YEAR REAL-WORLD DATA ON ACUTE MYELOID LEUKEMIA: RETROSPECTIVE STUDY FROM PUBLIC HEALTH CENTER IN BRAZIL
Authors: Felipe Feistauer, Marco Salvino, Marianna Batista, Lúcia Noblat
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) is a heterogeneous aggressive leukemia with poor prognosis. The standard remission induction regimen for medically eligible patients with AML consists of a backbone of cytarabine & an anthracycline (“7 + 3” therapy). Brazil is a large country with striking differences in in climate, ethnic heterogeneity and socioeconomic factors. Aims: To assess effectiveness (Eligible to the Next Treatment-ENT CR and suficient performance status to the next treatment, PFS and OS) and security (Early Mortality) of cytarabine and anthracycline (“7 + 3”regimen) in a public health center in Salvador, Brazil. Subgroups analyzed were about FTL3 and NPM1 mutations, leukocytes (>10,000 or <10,000), platelets (>20,000 or <20,000), and transplanted or non-transplanted. Methods: It was a retrospective analysis of all the cases of non-promyelocytic AML diagnosed between 2018 and 2022 in the University Hospital Professor Edgar Santos of Federal University of Bahia, after being approved by the Ethics Committee of the hospital. Kaplan-Meier methods were used to determine the median of the time to OS and PFS. Results: A total of 45 patients were analyzed. Median age at diagnosis was 43 years (range, 16-69 years) with 62% females. There were 21% and 11% patients with FLT3-ITD and NPM1 mutations, respectively. Only 14 patients had karyotype test (85% with normal karyotype). Regarding effectiveness, 52% of patients were eligible for the next therapy after complete remission (consolidation or stem cell transplantation). Refractory patients were 20%. Early (4 weeks) mortality was 28%. The median of PFS and OS were 3.6 and 8.2 months respectively. Patients with FLT3 mutation, platelet < 20.000 and leukocytes < 10.000 had poor outcomes. In AML patients after stem cell transplantation, PFS and OS were, respectively 20 and 43 months. Average waiting time for start induction therapy was 12 days.Figure 1: Overall survival of patients treated with 7 + 3 in health public center in Brazil Summary/Conclusion: The outcomes were consistent with the literature, adjusted for the population in question. Even with access to diagnostic tests (not common in Brazilian’s health public centers), patients did not have access to targeted therapies, with the 7 + 3 regimen being the only treatment for fit patients. To achieve complete remission followed consolidation/transplantation is still the BEST scenarios in AML eligible patients, but the improvement of access to diagnostic and treatment is still an unmet need. Disclosures No relevant conflicts of interest to declare. Keywords: Acute myeloid leukemia